Down-regulation of hepatic peripheral-type benzodiazepine receptors caused by acute lead intoxication

Abstract

In the present study we investigated the influence of acute lead poisoning upon the expression of benzodiazepine receptors. In addition, we examined if administration of PK 11195, an isoquinoline carboxamide derivative, to lead-poisoned rats could modulate the changes in receptor binding properties achieved by lead alone. Lead poisoning was ascertained by determination of urine σ-aminolevulinic acid levels and lead levels in rat livers. Scatchard analysis of saturation curves of [³H]PK 11195 binding to liver membranes of rats treated with lead alone or with both lead and PK 11195 showed an approximately two-fold decrease in receptor density in comparison with control groups. Peripheral benzodiazepine receptor density in the kidneys and adrenals of poisoned rats was not changed by lead intoxication per se or by coadministration of PK 11195. Scatchard analysis of saturation curves of [³H]Ro 15-1788 binding in rat cerebral cortex tissue showed no difference in the receptor density between the various groups. The K_d values of all organs were in the nanomolar range (1–4 nM). We conclude that PK 11195 is not a protective agent of hepatic peripheral benzodiazepine receptors in lead intoxication. Moreover, it causes over-accumulation of lead in hepatocytes in an unknown mechanism of action.